膝骨关节炎软骨基质刚度对线粒体形态异质性的影响  

Matrix Stiffness Affects Mitochondrial Heterogeneity of Tibial Plateau Chondrocytes in Knee Osteoarthritis

作　　者：阚天佑 侯伶俐 李汉骏 崔俊琪 王耀 孙林 王燎[1] 于志锋[1] 严孟宁[1] KAN Tianyou;HOU Lingli;LI Hanjun;CUI Junqi;WANG Yao;SUN Lin;WANG Liao;YU Zhifeng;YAN Mengning(Shanghai Key Laboratory of Orthopedic Implants,Department of Orthopedic Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China;Shanghai Institute of Precision Medicine,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China;Department of Pathology,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China;Clinical Stem Cell Research Center,Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200120,China)

机构地区：[1]上海交通大学医学院附属第九人民医院骨科,上海市骨科内植物重点实验室,上海200011 [2]上海交通大学医学院附属第九人民医院、上海精准医学研究院,上海200011 [3]上海交通大学医学院附属第九人民医院病理科,上海200011 [4]上海交通大学医学院附属仁济医院临床干细胞研究中心,上海200120

出　　处：《医用生物力学》2023年第3期521-527,共7页Journal of Medical Biomechanics

基　　金：国家自然科学基金项目(12172223,12272232);上海市自然科学基金项目(20ZR1432000)。

摘　　要：目的研究膝骨关节炎(osteoarthritis,OA)胫骨平台不同区域基质刚度的差异,及其对软骨和线粒体形态的影响。方法获取OA胫骨平台软骨标本用于纳米压痕测试、透射电镜拍摄以及组织学分析。利用纳米压痕检测OA胫骨平台不同区域软骨基质刚度,通过透射电镜观察不同区域软骨线粒体形态,定量分析线粒体平面面积、形状、嵴体积密度的变化。通过组织学染色观察OA胫骨平台不同区域软骨损伤情况。结果OA胫骨平台软骨损伤具有区域异质性,内侧胫骨平台软骨和线粒体损伤更重,同时基质刚度更高。OA评分与基质刚度呈正相关。OA评分与线粒体形态之间也有显著的相关性:OA评分越高,线粒体平面面积越大、越圆以及嵴体积密度越低。结论胫骨平台不同区域的差异揭示了软骨基质刚度、OA评分和线粒体形态学参数之间的相关性,软骨基质刚度增加可能是造成软骨细胞线粒体损伤的主要原因,进而加重了OA进展。Objective To investigate the difference of matrix stiffness in different regions of tibial plateau in osteoarthritis(OA)and its effects on morphology of the cartilage and mitochondria.Methods The tibial plateau cartilage specimens of OA were obtained for nanoindentation test,transmission electron microscopy and histological analysis.The stiffness of cartilage matrix in different regions of OA tibial plateau was detected by nano-indentation.The morphology of cartilage mitochondria in different regions was observed by transmission electron microscopy,and the changes of mitochondrial plane area,shape and ridge volume density were quantitatively analyzed.Cartilage injury in different regions of OA tibial plateau was observed by histological staining.Results The cartilage of OA tibial plateau showed regional heterogeneity,and the cartilage and mitochondria on medial side of varus knee OA were more severe,and the matrix stiffness was higher.The OA scores were positively correlated with matrix stiffness.There was also a significant correlation between OA scores and mitochondrial morphology:the higher OA scores,the larger and rounder mitochondrial plane area,and the lower cristae volume density.Conclusions The differences of tibial plateau revealed the correlation between cartilage matrix stiffness,OA scores and mitochondrial morphological parameters.The increased cartilage matrix stiffness may be the main cause of chondrocyte mitochondrial injury,and further aggravate the progression of OA.

关 键 词：骨关节炎 软骨细胞 线粒体 基质刚度 力学传导 

分 类 号：R318.01[医药卫生—生物医学工程]